Incorporation of a bromine atom into DNA-related molecules changes their electronic properties

Hirato, Misaki*; Yokoya, Akinari*; Baba, Yuji*; Mori, Seiji*; Fujii, Kentaro*; Wada, Shinichi*; Izumi, Yudai*; Haga, Yoshinori

Physical Chemistry Chemical Physics, 25(21), p.14836 - 14847, 2023/05

https://doi.org/10.1039/D3CP01597A

An Analytical method for quantifying the yields of DNA double-strand breaks coupled with strand breaks by -H2AX focus formation assay based on track-structure simulation

Yachi, Yoshie*; Matsuya, Yusuke*; Yoshii, Yuji*; Fukunaga, Hisanori*; Date, Hiroyuki*; Kai, Takeshi

International Journal of Molecular Sciences (Internet), 24(2), p.1386_1 - 1386_14, 2023/01

https://doi.org/10.3390/ijms24021386

When living cells are irradiated with radiation and complex damage is formed within a few nanometers of DNA, it is believed to induce biological effects such as cell death. In general, complex DNA damage formed in cells can be detected experimentally by fluorescence microscopy, because the area around the damage site emits light like a focus point when a fluorophore is used. However, this detection method has not been able to analyze the degree of complexity of DNA damage. Therefore, in this study, we addressed on the measured focus size and evaluated the degree of complexity of DNA damage using a track structure analysis code. As a result, we found that as DNA damage becomes more complex, the focus size also increases. Our findings are expected to provide a new analytical method for elucidating the initial factors of radiation biological effects.

Radon inhalation decreases DNA damage induced by oxidative stress in mouse organs via the activation of antioxidative functions

Kataoka, Takahiro*; Shuto, Hina*; Naoe, Shota*; Yano, Junki*; Kanzaki, Norie; Sakoda, Akihiro; Tanaka, Hiroshi; Hanamoto, Katsumi*; Mitsunobu, Fumihiro*; Terato, Hiroaki*; et al.

Journal of Radiation Research (Internet), 62(5), p.861 - 867, 2021/09

https://doi.org/10.1093/jrr/rrab069

Analysis of the high-dose-range radioresistance of prostate cancer cells, including cancer stem cells, based on a stochastic model

Saga, Ryo*; Matsuya, Yusuke; Takahashi, Rei*; Hasegawa, Kazuki*; Date, Hiroyuki*; Hosokawa, Yoichiro*

Journal of Radiation Research, 60(3), p.298 - 307, 2019/05

https://doi.org/10.1093/jrr/rrz011

In radiotherapy, it is recognized that cancer stem cells (CSCs) in tumor tissue shows radio-resistance. However, the relationship between content percentage of the CSCs and dose-response curve on cell survival remain unclear. In this study, we developed a stochastic model considering progeny cells and stem cells, and investigated the impact of stem cells on radio-sensitivity. From the flow-cytometric analysis (cell experiments), the content percentage of stem cells was 3.2% or less which agreed well with the model estimation from the cell survival curve. Based on the verification, it is suggested that cell survival in high-dose range is largely affected by the CSCs. In addition, regarding the sub-population of stem cells, the present model well reproduces the dose response on lethal lesions to DNA comparing with the conventional LQ model. This outcome indicates that the stem cells must be considered for describing the dose-response curve in wide dose range.

A Significant role of non-thermal equilibrated electrons in the formation of deleterious complex DNA damage

Kai, Takeshi; Yokoya, Akinari*; Ukai, Masatoshi*; Fujii, Kentaro*; Toigawa, Tomohiro; Watanabe, Ritsuko*

Physical Chemistry Chemical Physics, 20(4), p.2838 - 2844, 2018/01

https://doi.org/10.1039/C7CP06903K

It is thought that complex DNA damage which induces in radiation biological effects is formed at radiation track end. Thus, the earliest stage of water radiolysis at the electron track end was studied to predict DNA damage. These results indicate that DNA damage sites comprising multiple nucleobase lesions with a single strand breaks can therefore be formed by multiple collisions of the electrons within three base pairs (3bp) of a DNA strand. This multiple damage site cannot be processed by base excision repair enzymes. However, pre-hydrated electrons can also be produced resulting in an additional base lesion more than 3bp away from the multi-damage site. This clustered damage site may be finally converted into a double strand break (DSB) when base excision enzymes process the additional base lesions. These DSBs include another base lesion(s) at their termini that escape from the base excision process and which may result in biological effects such as mutation in surviving cells.

Reactivity of an antioxidant, edaravone, with reactive oxygen species and its chemical repair properties against oxidative damage on DNA

Hata, Kuniki; Lin, M.*; Yokoya, Akinari*; Fujii, Kentaro*; Yamashita, Shinichi*; Muroya, Yusa*; Katsumura, Yosuke*

Hoshasen Kagaku (Internet), (103), p.29 - 34, 2017/04

Reactivity of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), which is known to show high antioxidative properties, with oxidative species, such as hydroxyl radical (OH) and azide radical (N), was investigated by a pulse radiolysis experiment, and generation behavior of edaravone radicals produced through these reactions were observed. It was shown that OH-adducts are produced by the reaction with OH in contrast to the other oxidative radicals, which react with edaravone by an electron transfer reaction. Chemical repair properties of edaravone against DNA lesions produced by reactions of DNA with oxidative species were also investigated by a pulse radiolysis experiment with deoxyguanosine monophosphate (dGMP) and a -radiolysis experiment with plasmid DNA solutions. It was observed that edaravone reduced dGMP radicals just after produced in a dilute aqueous solution and inhibited some base lesions on plasmid DNA more effectively than single strand breaks. These results show that edaravone may protect living system from oxidative stress, such as radiation, by not only scavenging oxidative species but also reducing precursors of DNA leisons.

Evaluation of DNA damage induced by Auger electrons from Cs

Watanabe, Ritsuko; Hattori, Yuya; Kai, Takeshi

International Journal of Radiation Biology, 92(11), p.660 - 664, 2016/11

https://doi.org/10.3109/09553002.2015.1136853

To understand the effect of internal exposure of Cs, we focus on estimation of microscopic energy deposition pattern and DNA damage induced by directly emitted electrons (beta-rays, internal conversion electrons, Auger electrons) from Cs. Monte Carlo track simulation method was used to calculate the microscopic energy deposition pattern. To simulate the energy deposition by directly emitted electrons, we considered the multiple ejections of electrons after internal conversion. Induction process of DNA strand breaks and base lesions was modeled and simulated using Monte Carlo methods for cell mimetic condition. The yield and spatial distribution of simple and complex DNA damage were calculated for the cases of -rays and electrons from Cs. The simulation showed that significant difference of DNA damage spectrum was not caused by the difference between secondary electron spectrum by -rays and directly ejected electron spectrum. The result support that the existing evaluation that internal exposure and external exposure are almost equivalent.

DNA gyrase of is characterized as Type II bacterial topoisomerase and its activity is differentially regulated by PprA in vitro

Kota, S.*; Rajpurohit, Y. S.*; Charaka, V. K.*; Sato, Katsuya; Narumi, Issey*; Misra, H, S.*

Extremophiles, 20(2), p.195 - 205, 2016/03

https://doi.org/10.1007/s00792-016-0814-1

Dispersing zwitterions into comb polymers for nonviral transfection; Experiments and molecular simulation

Ghobadi, A. F.*; Letteri, R.*; Parelkar, S. S.*; Zhao, Y.; Chan-Seng, D.*; Emrick, T.*; Jayaraman, A.*

Biomacromolecules, 17(2), p.546 - 557, 2016/02

https://doi.org/10.1021/acs.biomac.5b01462

Molecular dynamics simulation of telomeric single-stranded DNA and POT1

Kaburagi, Masaaki; Yamada, Hironao*; Miyakawa, Takeshi*; Morikawa, Ryota*; Takasu, Masako*; Kato, Takamitsu*; Uesaka, Mitsuru*

Polymer Journal, 48(2), p.189 - 195, 2016/02

AA2015-0476.pdf:1.08MB

https://doi.org/10.1038/pj.2015.82

We performed molecular dynamics (MD) simulations of telomeric single-stranded DNA and POT1 for 100 ns. The distance between (POT1) and O5' (telomeric ssDNA) is calculated to verify the binding system for 100 ns MD. We then calculated the distance between the bases of telomeric DNA ends and the root mean square deviation and gyration radius in single and binding states. We compared the root mean square fluctuations between single and binding states and calculated the number of hydrogen bonds between POT1 and telomeric DNA. There are many hydrogen bonds between Gln94 and the first guanine of the closest TTAGGG sequence in telomeric single-stranded DNA. These Gln94 and the guanine have a large difference in root mean square fluctuation between single and binding states. We found that Gln94 and guanine are important components of the binding system, and they are related to its stability.